燃煤型砷中毒患者皮损PTCH基因D9S287和D9S180位点微卫星不稳定性的观察

目的观察燃煤型砷中毒患者皮损组织中PTCH基因微卫星DNA不稳定性及杂合性丢失与临床病理、临床分度之间的关系。方法选取D9S287、D9S180两个微卫星多态性标记,采用PCR扩增-变性聚丙烯酰胺凝胶电泳-银染法检测不同病理类型的燃煤型砷中毒患者的微卫星的改变。结果34例患者皮损组织PTCH基因微卫星不稳定性的发生率为29.41%(10/34),杂合性丢失的发生率为14.7%(5/34),微卫星的改变与病理分型相关(P<0.01),与临床分度无关(P>0.05)。结论PTCH基因微卫星不稳定性和杂合性丢失可能在砷中毒患者皮损癌变的发生发展中起重要作用。     

Apoptosis and its relationship with cell proliferation, p53, Waf1p21, bcl-2 and c-myc in esophageal carcinogenesis studied with a high-risk population in northern China

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Microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence

AIM： To investigate the microsatellite alterations in phenotypically normal esophageal squamous epithelium and metaplasia-dysplasia-adenocarcinoma sequence.
METHODS： Forty-one specimens were obtained from esophageal cancer （EC） patients. Histopathological assessment identified 23 squamous cell carcinomas （SCC） and 18 adenocarcinomas （ADC）, including only 8 ADC with Barrett esophageal columnar epithelium （metaplasia） and dysplasia adjacent to ADC. Paraffin-embedded normal squamous epithelium, Barrett esophageal columnar epithelium （metaplasia）, dysplasia and esophageal tumor tissues were dissected from the surrounding tissues under microscopic guidance. DNA was extracted using proteinase K digestion buffer, and DNA was diluted at 1：100, 1：1000, 1：5000, 1：10000 and 1：50000, respectively. Seven microsatellite markers （D2S123, D3S1616, D3S1300, D5S346, D17S787, D18S58 and BATRII loci） were used in this study. Un-dilution and dilution polymerase chain reactions （PCR） were performed, and microsatellite analysis was carried out.
RESULTS： No statistically significant difference was found in microsatellite instability （MSI） and loss of heterozygosity （LOH） of un-diluted DNA between SCC and ADC. The levels of MSI and LOH were high in the metaplasia-dysplasia-adenocarcinoma sequence of diluted DNA. The more the diluted DNA was, the higher the rates of MSI and LOH were at the above 7 loci, especially at D3S1616, D5S346, D2S123, D3S1300 and D18S58 loci.
CONCLUSION： The sequence of metaplasia-dysplasia-adenocarcinoma is associated with microsatellite alterations, including MSI and LOH. The MSI and LOH may be the early genetic events during esophageal carcinogenesis, and genetic alterations at the D3S1616, D5S346 and D3S123 loci may play a role in the progress of microsatellite alterations.     

Molecular analysis in combination with iodine staining may contribute to the risk prediction of esophageal squamous cell carcinoma

Purpose Mucosal iodine staining has improved the detection of precancerous lesions of the esophagus. However, this method is unable to exactly evaluate the risk status of the lesions. In the present study, we conducted a molecular analysis combining the iodine staining in esophageal squamous cell carcinomas (ESCC) and different premalignant lesions of the esophagus in order to improve the early diagnosis of ESCC. Methods Tumorous and precancerous lesions were procured as iodine-unstained areas in the resected specimens of ESCC patients by means of Lugol’s iodine staining. Loss of heterozygosity (LOH) was detected with 35 microsatellite markers frequently reported to be deleted in ESCC. The markers with high frequency of LOH in tumorous and precancerous lesions of the same patient were subjected to further detection in iodine-unstained biopsy samples from the population screening in ESCC high-incidence region. Results Common alterations were observed at D3S3644, D3S1768, D3S3040, D3S4542, RPL14, D9S169, D13S171 and D13S263 in both cancer tissues and precancerous lesions around tumors. Interestingly, D3S3644, D3S1768, D3S3040, D3S4542, RPL14 and D13S263 were also found with high frequency of LOH in iodine-staining abnormal lesions from the population screening. Most importantly, LOH frequency increased with histological severity. Conclusion Our data suggest that detection of these six markers in combination with iodine staining might contribute to the prediction for the risk of ESCC development and for the diagnosis of patients in preclinical and preneoplastic phase of the disease.     

老年人食管鳞状上皮化生和不典型增生及腺癌序列微卫星改变

目的评估老年人食管鳞状上皮和化生-不典型增生-腺癌的微卫星变化。方法应用稀释性聚合酶链反应（PCR）方法检测存档手术切除的食管癌标本中的D2S123、D3S1616、D3S1300、BATRII、D5S346、D17S787和D18S61位点微卫星的变化。结果在非稀释DNA中，17例食管鳞状细胞癌和12例腺癌微卫星不稳定性（MSI）的频率分别是52．9％（9例）和41．7％（5例），杂合性丢失（LOH）的频率分别是23．5％（4例）和16．7％（2例），两者差异均无统计学意义（P〉0．05）。在8例食管鳞状上皮和化生-不典型增生-腺癌组织稀释DNA中，MSI和LOH频繁出现，与其非稀释DNA的结果比较，差异均有统计学意义（P〈0．05）。结论MSI和LOH在上述组织中普遍存在，它们可能是食管腺癌发生、发展的早期事件。     

Genome-wide analyses on loss of heterozygosity in hepatocellular carcinoma in Southern China

BACKGROUND/AIMS: To conduct a genome-wide analysis of loss of heterozygosity (LOH) and its clinical significance in hepatocellular carcinoma (HCC) in Southern China where high incidence of HCC was documented. METHODS: LOH of 382 microsatellite loci on all autosomes were detected with polymerase chain reaction-based microsatellite polymorphism analyses in 104 HCC tumor tissues. RESULTS: High frequency of LOH (>55.7%) was observed on chromosome 1p, 1q, 2q, 3p, 4q, 6q, 8p, 9p, 13q, 16q, and 17p. LOH rates on loci D4S2964 (4q21.21), D8S277 (8p23.1-pter) and D17S938 (17p13.1-p13.3) were significantly higher in cases with positive HBsAg than in those with negative HBsAg. Similarly, LOH on loci D1S214 (lp36.3), D1S2797 (1p34) and D3S3681 (3p11.2-p14.2) were more frequently detected in tumors with intrahepatic metastasis than in those without. CONCLUSIONS: Status of LOH in HCC in Southern China is similar to that reported previously in other countries and areas. However, we firstly identified high-frequency LOH on chromosome 3p in HCC. Furthermore, HBV infection, as well as tumor intrahepatic metastasis, may be correlated with allelic losses on certain chromosome regions.     

Chromosome 9p deletion in squamous metaplasia in cystic lesion of the lung

A 70-year-old man presented with squamous cell carcinoma of the lung. Examination of the resected specimen showed a tumour and a thickly walled cyst not immediately adjacent to the main tumour. The surface of the cyst was lined by squamous metaplastic epithelium. Microsatellite analysis of microdissected specimens was performed with seven markers from four chromosomal regions. In the squamous cell carcinoma, a non-informative homozygosity at two markers on 3p, loss of heterozygosity (LOH) at D5S346 on 5q, and LOH at D9S146, D9S150, and D9S1748 on 9p were detected. In the metaplastic epithelium of the cyst, LOH was detected at D9S1748 on 9p21. This appears to be the first report providing possible evidence of genetic changes by demonstrating allelic loss on 9p21 in the metaplastic epithelium of a cyst. This allelic loss might be related to an early step in carcinogenesis in lung cysts.     

17号染色体微卫星不稳定性和杂合性丢失与非小细胞肺癌的关系

目的　明确１７ 号染色体微卫星不稳定性（ＭＩ） 和杂合性丢失（ＬＯＨ） 与非小细胞肺癌（ＮＳＣＬＣ） 的关系。方法　对３５ 例ＮＳＣＬＣ肿瘤切除组织和肿瘤旁正常组织,采用聚合酶链反应微卫星长度多态性分析方法检测了１７ 号染色体上４ 个微卫星位点ＴＰ５３（１７ｐ１３－１）、ＴＨＲＡ１（１７ｑ１１－２１２）、Ｄ１７Ｓ５７９（１７ｑ１２２１）、Ｄ１７Ｓ８５５（１７ｑ２１） 的ＭＩ和ＬＯＨ。结果　３５ 例ＮＳＣＬＣ中,１７ 号染色体ＭＩ和（或）ＬＯＨ的发生率为６３％ （２４／３５）,其中ＭＩ为４０％ （１４／３５） ,ＬＯＨ 为３１％ （１１／３５）。同时表现有ＭＩ和ＬＯＨ 为９％ （３／３５） 。早期ＮＳＣＬＣ（ Ⅰ期和Ⅱ期） １７ 号染色体ＭＩ和（ 或）ＬＯＨ 发生率为７９％ （１５／１９）,明显大于晚期（ Ⅲ期）ＮＳＣＬＣ（４４％ ,７／１６,Ｐ＜０－０５） 。无纵隔淋巴结转移的ＮＳＣＬＣ的ＭＩ和（ 或）ＬＯＨ 发生率（８７％ ） 亦明显大于已有纵隔淋巴结转移者（４８％ ）,Ｐ＜ ０－０５。ＭＩ和（ 或）ＬＯＨ 在不同肿瘤组织类型以及不同组织细胞分化程度之间差异无显著性,Ｐ＞０．０５。结论　１７ 号染色体ＭＩ和ＬＯＨ 在ＮＳＣＬＣ的发生中可     

Esophageal squamous cell carcinomas with DNA replication errors (RER+) are associated with p16/pRb loss and wild-type p53

PURPOSE: Microsatellite instability (MSI) as a determinant of propensity to esophageal squamous cell carcinoma (ESCC) at seven microsatellite markers at 2p (2p15-16), 3p (3p13, 3p14.1-3, 3p25, and 3p26) and 16q (16q12.1-3) was investigated to analyze their putative role as indicators of predisposition to esophageal malignancies. METHODS: Seven microsatellite loci were amplified by polymerase chain reaction, from surgically resected tumor tissues from 30 ESCC patients from Indian population, to assess the loss of heterozygosity (LOH) and replication error repeats (RER) and to correlate these alterations with aberrations in major cell cycle regulatory proteins and histopathological parameters. RESULTS: LOH and RER analyses at these loci demonstrated moderate microsatellite alterations, suggesting the involvement of MSI in esophageal tumorigenesis in a subset of the Indian population. MSI, defined as RER in at least two or more of the loci studied, was observed in ten of 30 (33%) patients. Twenty-two of 30 patients (73%) showed LOH at one or more loci, while 17 of the 30 patients (60%) showed RER in at least one of the loci studied. RER-positive patients showed a trend towards better prognosis when compared to RER-negative patients. MSI demonstrated a significant association with concomitant loss of p16 and pRb (p16-/pRb- phenotype) (P=0.046). Interestingly, we observed an inverse correlation between MSI and p53 mutations (P=0.03) suggesting that MSI may provide a p53-independent pathway for esophageal tumorigenesis in RER+ patients. MSI showed a trend towards longer survival and absence of distant organ metastasis (P=0.06). CONCLUSIONS: The present study demonstrates the probable role of MSI in esophageal squamous cell carcinoma in the Indian population. Instability associated with the repetitive sequences--the revealing marks of loss of DNA replication fidelity may serve as an indicator of predisposition to esophageal cancer.     

An early lesion in hepatic carcinogenesis: loss of heterozygosity in human cirrhotic livers and dysplastic nodules at the 1p36-p34 region

Loss of heterozygosity (LOH) of chromosome 1 has been suggested, by karyotyping, to be an initial episode in human hepatocarcinogenesis. However, this alteration has not yet been investigated in cirrhotic nodules (CNs) or dysplastic nodules (DNs). In an initial study from explanted or resected cirrhotic livers, LOH in 1p36-p32 was examined in 31 hepatocellular carcinomas (HCCs), 25 low-grade dysplastic nodules (LGDNs), and 24 high-grade dysplastic nodules (HGDNs). In HCCs, LOH was detected most frequently at loci D1S2843 (1p36.1) (28.6%), D1S513 (1p34.3) (29.2%), and MYCL1 (1p34.1) (28.6%). In HGDN and LGDN, LOH incidences at D1S513 were 11.1% and 13.6%, respectively. To further refine those results and to determine sequential relationships among CN, DN, and HCC, LOH was next studied in an additional 53 HCCs, 56 HGDNs, 30 LGDNs, and 215 CNs from 11 explanted human cirrhotic livers, including 30 "nodule-in-nodule" lesions. Seven markers between D1S2843 (1p36.12) and MYCL1 (1p34.1), and 1 each at D1S484 (1q24.1), IGF2R-3 (6q26), and TP53 (17p13.1) were used. LOH at D1S2843 and D1S513 was detected in HCCs (20.4% and 23.5%, respectively), HGDNs (7.7% and 18.5%), LGDNs (13.6% and 6.9%), and CNs surrounding either HCCs or DNs (7.4% and 8.3%). These results demonstrate that LOH at D1S2843 and D1S513 are early events in human liver carcinogenesis. Data from CN surrounding either HCCs or DN, and also nodule-in-nodule lesions, provide evidence supporting a CN-->DN-->HCC progression. Different deletion patterns from multiple HCCs and DNs suggest independent origins for carcinogenesis in the same individual.     

Tumor suppress genes screening analysis on 4q in sporadic colorectal carcinoma

AIM： To search candidate tumor suppressor genes （TSGs） on chromosome 4q through detecting high loss of heterozygosity （LOH） regions in sporadic colorectal carcinoma in Chinese patients. METHODS： Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction （PCR）. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ^2 test.
RESULTS： Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%, The D4S2915 locus showed highest LOH frequency （36.17%）. Two obvious deletion regions were detected： one between D4S3000 and D4S2915 locus （4q12-21.1）, another flanked by D4S407 and D4S2939 locus （4q25-31.1）. None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018 locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm （56% vs 13.79%, P = 0.01）. On D4S1534 locus, LOH was significantly associated with liver metastasis （80% vs 17.25%, P = 0.012）. No relationship was detected on other locus compared with clinicopathologial features.
CONCLUSION： By high resolution deletion mapping, two high frequency regions of LOH （4q12-21.1 and 4q25-31.1） were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.     

Loss of heterozygosity on chromosome 1 in sporadic colorectal carcinoma

AIM: Loss of heterozygosity (LOH) on tumor suppressor genes is believed to play a key role in carcinogenesis of colorectal cancer. When it occurs at a tumor suppressor gene locus with abnormal allele, neoplastic transformation happens. In this study, we analyzed the LOH at 21 loci on chromosome 1 in sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis. METHODS: Twenty-one polymorphic micro-satellite DNA markers were analyzed with PCR both in 83 cases of colorectal cancer and in normal tissues. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. chi2 test was used to compare LOH frequency with clinicopathological data. P<0.05 was considered as statistically significant. RESULTS: The average LOH frequency of chromosome 1, short arm and long arm was 19.83%, 18.00% and 21.66%, respectively. The 2 highest LOH loci with a frequency of 36.54% and 32.50% were identified on D1S468 (1p36.33-p36.31) and D1S413 (1q31.3), respectively. On D1S2726 locus, LOH frequency of rectal cancer was 28.57% (6/21), which was higher than that of colon cancer (0.00%, 0/33) (P=0.002), suggesting that the mechanism of carcinogenesis was different in both groups. CONCLUSION: Putative tumor suppressor genes on chromosome 1 may relate to sporadic colorectal carcinomas. Tumor-suppressor-genes might locate on 1p36.33-36.31 and/or 1q31.3.     

Loss of heterozygosity on long arm of chromosome 22 in sporadic colorectal carcinoma

AIM：The loss of heterozygosity(LOH)on tumor suppressor genes is believed to play a key role in carcinogenesis of colorectal cancer.In this study,we analyzed the LOHat5loci on the 1ong arm of chromosome22in sporadic colorectal cancer to identify additional loci involved in colorectal tumorigenesis.METHODS:Five poly morphic microsatellite markers were analyzed in 83cases of colorectal and normal DNAby PCR.PCRproducts were eletrophoresed on an ABI377DNA sequencer;Genescan3.1and Genotype2.1software were used for LOH scanning and analysis.Comparison between LOH frequency and clinicopathological data were performed by X^2test.P&lt;0.05was considered as statistically significant.RESULTS:The average LOHfrequency on chromosome 22q was 28.38%.The region between markers D22S280and D22S274(22q12.2-q13.33)exhibited relatively high LOH frequency.The two highest LOH loci with frequencies of 35.09%and 34.04%was identified on D22S280(22q12.2-12.3)and D22S274(22q13.32-13.33).8cases showed LOH at allinformative loci,suggesting that one chromosome 22q had been completely lost.On D22S274locus.LOH frequency of rectal cancer was50%(9/18),which was higher than that of proximal colon cancer(12%,2/17)(P=0.018).The frequency of distal colon cancer was 42%(5/12).also higher than that of proximal colon cancer.But there was no statistical significance.Putting both the tumors in distal colon and rectm together into consideration.the frequency,47%(14/30),was higher than that of proximal colon cancer(P=0.015),suggesting the mechanism of carcinogenisis was diffenent in both groups.CONCLUSIONS:This study provided evidence for the involvement of putative tumor suppressor genes related to the sporadic colorectal carcinoma on chromosome 22q.The tumor-suppressor-gene(s)might locate on the 22q12.2-12.3and/or 22q13.32-13.33.     

Frequency of loss of heterozygosity at 3 p, 9 p, 13 q, and 17 p is related to proliferative activity in smokers with stage I non-small cell lung cancer

BACKGROUND: Tumor cells of lung cancer exhibit genetic abnormalities as well as high proliferative activity. The purpose of this study was to evaluate the relationship of genetic abnormalities and smoking status, histological type, and tumor proliferative activity in resected samples of stage I non-small cell lung cancer (NSCLC). METHODS: We evaluated 126 samples of stage I NSCLC from patients who underwent complete resection between 1988 and 1993. Loss of heterozygosity (LOH) was assessed using primers that amplified polymorphic microsatellite markers at D3S1300, D3S643, D3S1317, D9S171, IFNA, D13S153, and TP53. Expression of Ki-67 nuclear antigen was examined using immunohistochemical methods to assess tumor proliferative activity. RESULTS: The Fractional Regional Loss index (FRL) was significantly higher in squamous cell carcinoma samples than in adenocarcinoma samples (p < 0.0001). In smokers, Ki-67 labeling index (LI) in high-FRL cases was significantly higher than in low-FRL cases (p < 0.0001). CONCLUSION: The frequency of LOH at 3 p, 9 p, 13 q, and 17 p was related to proliferative activity in smokers with stage I non-small cell lung cancer.     

Allelotyping for loss of heterozygosity on chromosome 18 in gastric cancer

AIM: To investigate the association between loss of heterozygosity (LOH) on chromosome 18 and sporadic gastric cancer. METHODS: Multiplex PCR was used to screen 14 highly polymorphic microsatellite markers on chromosome 18 in 45 cases of primary gastric cancer. PCR products were separated on polyacrylamide gels and the electrophoresis maps were analyzed with Genescan and Genotyper. RESULTS: The LOH frequencies in gastric cancer at all 14 markers ranged from 10% to 58%. Eleven markers were found with over 20% LOH frequencies, in which 9 markers located in 18q, and 2 markers in 18p. Two overlapping deleted regions were identified: R1 between D18S61-D18S1161 at 18q22 (9cM) with 24% LOH frequency; R2 between D18S462-D18S70 at 18q22-23(6cM) with 32% LOH frequency. CONCLUSION: LOH of chromosome 18 (18q and 18p) may be involved in gastric tumorigenesis. Two overlapping deleted fragments suggested that there might be unidentified tumor suppressor genes in those two regions.     

Changes in p53 and Waf1p21 expression and cell proliferation in esophageal carcinogenesis

AIM: To study the correlation between changes in p53 and Waf1p21 expression and cell proliferation, determined by proliferating cell nuclear antigen (PCNA), at different stages of human esophageal carcinogenesis.METHODS: Biopsied and resected esophageal tissues from a high risk population of esophageal cancer in northern China were used in this study. All specimens were fixed in 85% alcohol and processed for routine histology. The avidin biotin peroxidase complex (ABC) method was used to detect p53, Waf1p21 and PCNA.RESULTS: Strong nuclear staining of p53, Waf1p21 and PCNA was observed in normal esophageal epithelium and epithelia with different lesion severities. As the lesions progressed to dysplasia (DYS) and to esophageal squamous cell carcinoma (SCC), the Waf1p21 immunoreactivity percentage decreased. The number of Waf1p21-positive cells slightly increased from normal to basal cell hyperplasia (BCH), but did not further increase in DYS and SCC. The total number of Waf1p21-positive cells was lower than the number of p53-positive cells in normal and BCH esophageal epithelia and much lower in DYS and SCC. Waf1p21-positive cells were located in the third and fourth cell layers in half of the samples examined, which was 2-4 cell layers higher than the cells expressing PCNA and p53 in the same histological categories of normal, BCH and DYS.CONCLUSION: Low Waf1p21 levels at the DYS stage may be related to a functional loss of p53. Other mechanisms may also be responsible for the decreased Waf1p21 expression in DYS and SCC.     

Identification of minimal regions of deletion at 8p23.1-22 associated with metastasis of hepatocellular carcinoma.

AIMS/BACKGROUND: Loss of heterozygosity (LOH) at 8p is the most frequent chromosomal alteration in tumorigenesis of human cancers. However, the genetic change in metastasis of hepatocellular carcinoma (HCC) still has to be investigated. METHODS: We used 16 microsatellite markers informative in Japanese patients, selected from among 61 published microsatellite markers at 8p23.2-21 to compare the frequency of LOH in primary tumours (Tps) and metastatic tumours (Tms) in a PCR-based analysis. Sixty-three informative cancerous lesions (26 were Tps, 37 were Tms) from 23 cases of HCC were used. RESULTS: The frequency of LOH at 8p23.2-21 with at least one marker was 19% in Tps and 68% in Tms. Allelic loss at 8p23.2-21 was significantly more frequent in Tms than in Tps (P=0.0003). More specifically, the frequency of LOH at D8S262, D8S1819, D8S503, D8S1130, D8S552, D8S1109, and D8S261 in Tms was 36-60% respectively. CONCLUSIONS: In contrast, allelic loss at the same markers in Tp was only detected in 0-17% of the tumour respectively. The significant difference in the frequency of LOH at 8p between primary cancer and metastatic cancer in individual cases of HCC suggests LOH at 8p to be involved in the enhancement of tumour aggressiveness, especially during metastasis.     

Loss of heterozygosity on chromosome 10q22-10q23 and 22q11.2-22q12.1 and p53 gene in primary hepatocellular carcinoma

AIM: To analyze loss of heterozygosity (LOH) and homozygous deletion on p53 gene (exon2-3, 4 and 11), chromosome 10q22-10q23 and 22q11.2 -22q12.1 in human hepatocellular carcinoma (HCC). METHODS: PCR and PCR-based microsatellite polymorphism analysis techniques were used. RESULTS: LOH was observed at D10S579 (10q22-10q23) in 4 of 20 tumors (20%), at D22S421 (22q11.2-22q12.1) in 3 of 20(15%), at TP53.A (p53 gene exon 2-3) in 4 of 20(20%), at TP53.B (p53 gene exon 4) in 6 of 20(30%), and at TP53.G (p53 gene exon 11) in 0 of 20(0%). Homozygous deletion was detected at 10q22-10q23(8/20; 40%), 22q11.2-22q12.1(8/20; 40%), p53 gene exon 2-3(0/20;0%), p53 gene exon 4(6/20; 30%), and p53 gene exon 11(2/20; 10%). CONCLUSION: There might be unidentified tumor suppressor genes on chromosome 10q22-10q23 and 22q11.2-22q12.1 that contribute to the pathogenesis and development of HCC.     

Clinicopathological significance of loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in China

AIM: To determine the features of microsatellite alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC). METHODS: Loss of heterozygosity (LOH) and microsatellite instability (MSI) of 55 microsatellite loci were detected with PCR-based microsatellite polymorphism analyses in tumors and corresponding noncancerous liver tissues of 56 surgically resected HCCs using the MegaBACE 500 automatic DNA analysis system. RESULTS: LOH was found in 44 of 56 HCCs (78.6%) at one or several loci. Frequencies of LOH on 1p, 4q, 8p, 16q, and 17p were 69.6% (39/56), 71.4% (40/56), 66.1% (37/56), 66.1% (37/56), and 64.3% (36/56), respectively. MSI was found in 18 of 56 HCCs (32.1%) at one or several loci. Ten of fifty-six (17.9%) HCCs had MSI-H. Serum HBV infection, alpha-fetoprotein concentration, tumor size, cirrhosis, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with LOH on certain chromosome regions. CONCLUSION: Frequent microsatellite alterations exist in HCC. LOH, which represents a tumor suppressor gene pathway, plays a more important role in hepatocarcin-ogenesis. MSI, which represents a mismatch repair gene pathway, is a rare event during liver carcinogenesis. Furthermore, LOH on certain chromosome regions may be correlated with clinicopathological characteristics in HCC.